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Latest Research on Uveitis
     
Rheumatology (Oxford). 2008 Mar;47(3):339-44. Epub 2008 Jan 31.
Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis.
Tynjälä P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, Lahdenne P.
Department of Pediatric Rheumatology, Hospital for Children and Adolescents, Helsinki, Finland. pirjo.tynjala@hus.fi

OBJECTIVE: To evaluate the efficacy of adalimumab in juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: Retrospective observational study of 20 patients with JIA and chronic uveitis on adalimumab treatment. The ocular inflammation and improvement was assessed according to the Standardization of Uveitis Nomenclature criteria. RESULTS: At the initiation of adalimumab, the mean age of patients was 13.4 yrs and the mean duration of uveitis 8.7 yrs. Seventeen (85%) patients had polyarticular JIA and 19 (95%) had previously been on anti-TNF treatment. The mean duration of adalimumab therapy was 18.7 months. Of the 20 patients, 7 (35%) showed improved activity, 1 (5%) worsening activity and in 12 (60%) no change was observed in the activity of uveitis. Those with improved activity were younger and had shorter disease duration. The mean number of flares/yr decreased from 1.9 to 1.4 during adalimumab treatment. Serious adverse events or side-effects were not observed. Seven patients discontinued adalimumab during the follow-up: six because of inefficacy and one because of inactive uveitis. CONCLUSION: Adalimumab is a potential treatment option in JIA-associated uveitis, even in patients non-responsive to previous other anti-TNF therapy.

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Int Ophthalmol. 2008 Feb 23 [Epub ahead of print]
Long-term control of cystoid macular oedema in noninfectious uveitis with Mycophenolate Mofetil.
Neri P, Mariotti C, Cimino L, Mercanti L, Giovannini A.
Neuroscience Department, Ophthalmology Section, Polytechnic University of Marche, Via Tronto 10, Torrette, Ancona, Italy, doctor_blacks@hotmail.com.

Purpose To evaluate the long-term safety and efficacy of Mycophenolate Mofetil (MMF) for the control of cystoid macular oedema (CMO) secondary to noninfectious uveitis (NU). Methods The medical records of 19 consecutive patients with inflammatory CMO treated with MMF were retrospectively reviewed. Patient demographics, best corrected visual acuity (BCVA), fluorescein angiography (FA), and optical coherence tomography (OCT) findings were evaluated. Results There were eight females and 11 males with a mean age of 32.9 +/- 8.9 years. After a 1-year follow-up, 18/19 patients (31 eyes, 96.9%, P < 0.05) no longer had signs of CMO, as per their FA and OCT findings; the mean central foveal thickness (CFT) was 167.2 +/- 12.8 mum. At the last follow-up, only 3/19 patients, all affected by Behçet panuveitis, had recurrences of CMO. Mean BCVA improved from 0.34 +/- 0.14 SD at baseline to 0.65 +/- 0.2 SD at last follow-up. Conclusions MMF was safe and effective in controlling CMO and in reducing the uveitis relapse rate in patients not responding to traditional immunosuppressants. Further case-controlled studies are mandatory to validate those preliminary results.

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Arch Ophthalmol. 2008 Feb;126(2):200-5.
Short-term safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular edema in children.
Sallam A, Comer RM, Chang JH, Grigg JR, Andrews R, McCluskey PJ, Lightman S.
Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye Hospital, City Road, London EC1V 2PD, England.

OBJECTIVES: To evaluate the short-term safety and efficacy of intravitreal (IV) triamcinolone acetonide (TA) for treating pediatric cystoid macular edema (CME) secondary to noninfectious uveitis. METHODS: A retrospective noncomparative interventional case series. The medical records of 15 consecutive children (16 eyes) with uveitic CME treated with IVTA (2 or 4 mg) were reviewed. Data collected included details of uveitis, CME, visual acuity, intraocular pressure, and cataract development. The median follow-up time was 16 months (range, 9-36 months). RESULTS: Resolution of CME was achieved in all of the treated eyes. The median time taken for CME to resolve was 3 weeks (range, 1-24 weeks). The mean improvement of visual acuity after IVTA was 0.6 logarithm of the minimum angle of resolution. Following initial response to IVTA, CME relapsed in 5 eyes (31%) after a median time of 7 months (range, 3-13 months). The most common adverse effect was increased intraocular pressure, with an increase of more than 15 mm Hg in 5 eyes (31%). Steroid-induced cataract was observed in 6 of 11 phakic eyes (55%). CONCLUSIONS: We found that IVTA is efficacious in the treatment of uveitic CME in children and results in CME resolution and visual acuity improvement. As in adults, treatment in children may be associated with elevated intraocular pressure and cataract.

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Am J Ophthalmol. 2008 Jan 26 [Epub ahead of print]
Reimplantation of a Fluocinolone Acetonide Sustained Drug Delivery Implant for Chronic Uveitis.
Jaffe GJ.
Duke Eye Center, Duke University Medical Center, Durham, North Carolina.

PURPOSE: To determine the effects of a second fluocinolone implant inserted in eyes with uveitis in which recurrent inflammation developed after the original implant was placed. DESIGN: Prospective, interventional trial. METHODS: Study subjects comprised all consecutive patients with noninfectious posterior uveitis who were treated at the Duke Eye Center from March 2004 to July 2007, and followed for at least nine months, in whom a fluocinolone acetonide implant was initially inserted, and in whom the implant was replaced, or a second implant was inserted because of recurrent inflammation. The main outcome measures were inflammation recurrences, use of adjunctive anti-inflammatory therapy, visual acuity, intraocular pressure (IOP), and adverse events. RESULTS: Seventeen eyes of 14 patients were studied. The mean time from original fluocinolone implantation to first uveitis recurrence was 38 months. The time from first inflammation recurrence to the second implantation was eight months. The average follow-up was 17 months. Inflammation developed in only one eye during follow-up, three years after the second fluocinolone implant insertion. Adjunctive steroid use was decreased significantly. The mean snellen visual acuity 12 months after the second implant insertion was 20/78, compared with 20/400 at the time of the original fluocinolone implant placement (P = .04). The average IOP was unchanged after surgery compared with the preoperative IOP. CONCLUSIONS: The fluocinolone implant controls ocular inflammation for an average of three years after initial insertion. After the implant is depleted of drug, inflammation may recur. Placement of a new implant maintains the eye in a quiet state and stabilizes or improves visual acuity for an extended time. Adverse events during insertion of a new implant are uncommon.

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Klin Monatsbl Augenheilkd. 2008 Jan;225(1):66-9.
[Mycophenol Acid in Ocular Automimmune Disorders - Can We Optimise this Therapy?]
[Article in German]
Pleyer U, Ruokonen P, Schmidt N, Feist E, Höhne M, Stanojlovic S.
Universitäts-Augenklinik, Charité Campus Virchow-Klinik, Berlin.

BACKGROUND: Mycophenolate mofetil (MMF) has gained acceptance as an immune modulatory agent in the treatment of autoimmune disorders such as uveitis. It represented a major advance, although optimal use may be limited, in particular, by gastrointestinal (GI) side effects in up to 50 % patients. This prospective study was undertaken to evaluate the effect of conversion from mycophenolate mofetil (MMF) to an enteric-coated mycophenolate sodium (EC-MPS). PATIENTS AND METHODS: Within a cohort of 143 patients treated with MMF we prospectively followed 19 inidviduals who developed gastrointestinal side effects. Because of limited treatment alternatives, conversion to an enteric-coated mycophenolate sodium (EC-MPS) was undertaken. A standardised questionnaire (GSRS) was completed by each patient regarding GI adverse events, at predefined intervals during the study. RESULTS: The spectrum of underlying disorders included uveitis (n = 16) and ocular cicatricial pemphigoid (n = 3) that
were initially treated with MMF (1000 mg BID). All patients could be kept on EC-MPS treatment and followed with a mean follow-up of 44 weeks (median +/- 12). The maximum of scores on GSRS was reached at baseline (conversion to EC-MPS) in all but 3 patients. However, GSRS scores improved significantly between baseline and visit 4 (3 months) and remained stable further on (p < 0.03). In all but one (uveitis) patient the underlying disorders were under control demonstrating the similar efficacies of MMF and EC-MPS teatments. CONCLUSION: The use of EC-MPS appears to be a valid treatment option in ocular autoimmune disorders. In particular. patients with gastrointestinal problems may profit from a significantly reduced frequency of adverse events.

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Ophthalmology. 2008 Jan 24 [Epub ahead of print]
Mycophenolate Mofetil after Methotrexate Failure or Intolerance in the Treatment of Scleritis and Uveitis.
Sobrin L, Christen W, Foster CS.
Massachusetts Eye Research and Surgery Institute, Cambridge, Massachusetts.

PURPOSE: To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Eighty-five patients with scleritis and/or uveitis who failed with or did not tolerate methotrexate and were subsequently treated with mycophenolate mofetil between 1998 and 2006. METHODS: We reviewed medical records of patients who were treated with mycophenolate mofetil after methotrexate intolerance or failure at one tertiary uveitis referral practice. We recorded dose and duration of methotrexate and mycophenolate mofetil therapy, inflammation grade, Snellen visual acuity (VA), use of other immunomodulatory therapy, and adverse events. Multivariate logistic regression was used to identify factors associated with inflammation control. MAIN OUTCOME MEASURES: Control of inflammation, steroid-sparing effect, VA, and adverse effects were assessed. RESULTS: Inflammation was controlled with mycophenolate mofetil in 47 patients (55%), with 5 achieving durable remission off all medication. In multivariate logistic regression analysis that adjusted for gender and age, the odds of inflammation control were lower for patients with scleritis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.04-0.93; P = 0.04) than for patients without scleritis. Among patients without scleritis, the odds of inflammation control were lower for patients with juvenile idiopathic arthritis (JIA)-associated uveitis (OR, 0.14; CI, 0.02-0.81, P = 0.03) compared to patients without JIA-associated uveitis. Eight of the 11 patients (73%) who were taking concomitant prednisone were able to taper their dose to <10 mg daily. Visual acuity declined in a greater percentage of patients who were unresponsive to mycophenolate mofetil (29%) compared with that of patients who responded to mycophenolate mofetil (9%). Side effects requiring discontinuation of mycophenolate mofetil occurred in 18 patients (21%). CONCLUSIONS: Mycophenolate mofetil was effective in controlling inflammation in approximately half of the patients who had previously failed with or did not tolerate methotrexate. The odds of inflammation control were less in patients with the diagnoses of scleritis and JIA.

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Am J Ophthalmol. 2007 Dec;144(6):844-849. Epub 2007 Oct 22.
Infliximab to Treat Chronic Noninfectious Uveitis in Children: Retrospective Case Series with Long-term Follow-up.
Ardoin SP, Kredich D, Rabinovich E, Schanberg LE, Jaffe GJ.
Division of Pediatric Rheumatology, Duke University Medical Center, Durham, North Carolina.

PURPOSE: To assess a response to infliximab therapy in childhood uveitis. DESIGN: Retrospective case series. METHODS: We reviewed the course of 16 children with noninfectious uveitis treated with infliximab at an academic medical center. Outcome measures included incidence of uveitis recurrences, proportion of patients achieving zero or two-step decline in ocular inflammation, visual acuity, and proportion discontinuing topical glucocorticoids at zero, three, six, nine, and 12 months of therapy. RESULTS: Of sixteen children (29 affected eyes) with median age 11 years, six had associated extraocular inflammatory conditions. Fifteen of 16 were treated with concomitant methotrexate. Median follow-up was 26 months and median maintenance infliximab dose was 8.2 mg/kg. The median interval between infliximab infusions was 5.6 weeks. At one year, 64% achieved zero ocular inflammation, and 79% had zero inflammation or a two-step decline in inflammation. Topical glucocorticoids were discontinued in 69%, and 58% remained free of uveitis recurrence at one year. Visual acuity remained stable. Infliximab was discontinued in two children, one because of inefficacy and the other because of parental concern about potential side effects. No adverse events occurred. CONCLUSIONS: Sixteen children with chronic, noninfectious uveitis tolerated chronic methotrexate and infliximab therapy. Visual acuity remained stable, control of ocular inflammation improved, and reliance on topical glucocorticoids decreased. High infliximab doses and frequent dosing intervals were necessary to control uveitis.

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Acta Ophthalmol Scand. 2007 Nov 6 [Epub ahead of print]
Fuchs' heterochromic uveitis: a longitudinal clinical study.
Norrsell K, Sjödell L.
Department of Ophthalmology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Purpose: To carry out a longitudinal study of patients with Fuchs' heterochromic uveitis (FHU) in western Sweden and to establish the factors responsible for diagnostic delay. Methods: A sample of 54 patients, 51 with monocular and three with binocular FHU, were followed for periods ranging from 8 months to 15 years. Firm diagnostic criteria were set. A detailed anamnesis regarding ocular and extraocular symptoms was taken. The eyes were repeatedly examined. Toxoplasma serology was analysed. Complications were noted. Results: The delay between the first visit to an ophthalmologist and diagnosis was 0-26 years. The most common first symptom was floaters. Iris heterochromia was absent in 11 patients and discrete in 26. Iris atrophy (a diagnostic criterion) was easy to miss. Chorioretinal scars were found in six patients. Toxoplasma serology was positive in 18 (35%) patients. The only serious complication was glaucoma. Conclusions: The most important reason for delay in diagnosis of FHU is, in our opinion, failure to consider the disease as a diagnosis. This failure may occur because heterochromia is often missing or discrete, iris atrophy is easily overlooked, and vitreous opacities are common, often cause early symptoms and can explain prolonged workup and therapy. A connection with toxoplasmosis in individual cases cannot be excluded but toxoplasmosis cannot be considered a major aetiological factor. If detailed anamnesis is negative and diagnostic criteria are fulfilled, no further workup is required.

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Clin Immunol. 2007 Oct 2 [Epub ahead of print]
TNFalpha blockade in human diseases: An overview of efficacy and safety.
Lin J, Ziring D, Desai S, Kim S, Wong M, Korin Y, Braun J, Reed E, Gjertson D, Singh RR.
UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.

Tumor necrosis factor-alpha (TNFalpha) antagonists including antibodies and soluble receptors have shown remarkable efficacy in various immune-mediated inflammatory diseases (IMID). As experience with these agents has matured, there is an emerging need to integrate and critically assess the utility of these agents across disease states and clinical sub-specialties. Their remarkable efficacy in reducing chronic damage in Crohn's disease and rheumatoid arthritis has led many investigators to propose a new, 'top down' paradigm for treating patients initially with aggressive regimens to quickly control disease. Intriguingly, in diseases such as rheumatoid arthritis and asthma, anti-TNFalpha agents appear to more profoundly benefit patients with more chronic stages of disease but have a relatively weaker or little effect in early disease. While the spectrum of therapeutic efficacy of TNFalpha antagonists widens to include diseases such as recalcitrant uveitis and vasculitis, these agents have failed or even exacerbated diseases such as heart failure and multiple sclerosis. Increasing use of these agents has also led to recognition of new toxicities as well as to understanding of their excellent long-term tolerability. Disconcertingly, new cases of active tuberculosis still occur in patients treated with all TNFalpha antagonists due to lack of compliance with recommendations to prevent reactivation of latent tuberculosis infection. These safety issues as well as guidelines to prevent treatment-associated complications are reviewed in detail in this article. New data on mechanisms of action and development of newer TNFalpha antagonists are discussed in a subsequent article in the Journal. It is hoped that these two review articles will stimulate a fresh assessment of the priorities for research and clinical innovation to improve and extend therapeutic use and safety of TNFalpha antagonism.

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Eur J Ophthalmol. 2007 Sep-Oct;17(5):743-8.
Methotrexate for uveitis associated with juvenile idiopathic arthritis: value and requirement for additional anti-inflammatory medication.
Heiligenhaus A, Mingels A, Heinz C, Ganser G.
Department of Ophthalmology, St. Franziskus Hospital, Muenster, Germany. arnd.heilingenhaus@uveitis-zentrum.de

PURPOSE: To study the value of methotrexate (MTX) and the requirement for additional anti-inflammatory drugs for the treatment of severe chronic iridocyclitis associated with juvenile idiopathic arthritis (JIA). METHODS: Institutional study of 35 consecutive patients with JIA started on MTX as the single systemic immunosuppressive drug for the treatment of associated iridocyclitis. The clinical epidemiologic data, course of visual acuity (VA), development of complications, and the need for additional anti-inflammatory drugs were analyzed. RESULTS: Mean follow-up with MTX treatment was 27.6 months. Uveitic complications were present in 31 patients before MTX treatment. With MTX, quiescence of uveitis was obtained with (n=21) or without (n=4) additional topical steroids. Additional systemic immunosuppressive drugs were required in another 7 patients: cyclosporine A (n=4), azathioprine (n=1), infliximab (n=1), or etanercept (n=1). Three patients had active uveitis at the end of the follow-up period. During MTX therapy, uveitis first developed in the unaffected fellow eyes in 2 patients, and secondary glaucoma or ocular hypertension occurred in 7 patients. The VA deteriorated in 6, improved in 13, and was stable in the remaining eyes. CONCLUSIONS: The data suggest that MTX is very effective in controlling inflammation of uveitis in patients with JIA. However, additional topical steroids or systemic immunosuppressive drugs are often required.

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Eur J Ophthalmol. 2007 Sep-Oct;17(5):733-42.
Control of inflammation and prophylaxis of endophthalmitis after cataract surgery: a multicenter study.
Camesasca FI, Bianchi C, Beltrame G, Caporossi A, Piovella M, Rapisarda A, Tassinari G, Zeppa L; Italian Betamethasone-Chloramphenicol vs Dexamethasone-Tobramycin Combination Study Group.
Department of Ophthalmology, Istituto Clinico Humanitas, Rozzano, Milano, Italy. fabrizio.camesasca@tiscali.it

PURPOSE: To compare two different postcataract surgery antibiotic/steroid therapeutic combinations, for clinical results as well as patient satisfaction. METHODS: Prospective randomized clinical trial of patients with bilateral operative cataract. Postoperatively, for 15 days one eye was randomly assigned to therapy with the combination chloramphenicol 0.25%-betamethasone 0.13% gel three times a day (Group 1) and the other to the combination tobramycin 0.3%-dexamethasone 0.1% eyedrops four times a day (Group 2). RESULTS: A total of 142 patients (284 eyes) completed the study. The authors could not detect any significant difference between Group 1 and Group 2 concerning preoperative evaluation, surgical procedure, and complications. Pertaining to the two therapeutic regimens, efficacy, side effects, and clinical findings such as uncorrected visual acuity, intraocular pressure, edema or hyperemia of eyelids and/or conjunctiva, conjunctival and/or ciliary vessels congestion, decreased corneal transparency, corneal edema, Descemet folds, anterior chamber Tyndall and depth, and posterior synechiae were also comparable. Postoperative subjective pain and dry eye sensation were comparable between the two groups, while the gel preparation elicited a significantly more pleasant sensation in the patients (p=0.04). CONCLUSIONS: The motivation for use of a gel is to prolong the permanence of associated drugs on the ocular surface, increasing potency and decreasing concentration of the drug and rate of administration. This in order to improve compliance and decrease potential side effects. Chloramphenicol 0.25%-betamethasone 0.13% gel combination proved to have comparable efficacy, tolerance, and better acceptance by the patients than an aqueous tobramycin 0.3%-dexamethasone 0.1% preparation.

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Arch Ophthalmol. 2007 Jul;125(7):895-900.
Infliximab therapy for the treatment of refractory ocular inflammatory disease.
Sobrin L, Kim EC, Christen W, Papadaki T, Letko E, Foster CS.
Massachusetts Eye Research and Surgery Institute, Cambridge, MA 02142, USA.

OBJECTIVE: To report the outcomes of infliximab therapy in the treatment of ocular inflammatory disease refractory to traditional immunomodulatory therapy (IMT). METHODS: We retrospectively reviewed the medical records of 27 patients. All patients had noninfectious ocular inflammatory disease refractory to traditional IMT and received 5 mg/kg of infliximab at 2-week to 8-week intervals. Main outcome measures were clinical response, reduction in concomitant IMT, and adverse effects. Cumulative incidences of inflammation control and vision change were calculated using life-table methods. RESULTS: Twenty-one patients experienced sustained improvement in inflammation with their initial course of infliximab therapy. Cumulative incidence of inflammation resolution at 12 months was greater than 90%. Sixteen patients were able to decrease the dose of their concomitant IMT medication or stop all other IMT. Four patients were able to discontinue all other IMT while receiving infliximab therapy. Three patients with scleritis were eventually able to remain inflammation-free while not taking any medication. At 12 months, 56% and 65% of left and right eyes, respectively, showed visual acuity improvement by 2 or more Snellen lines. Only 1 patient developed an adverse event requiring therapy discontinuation. CONCLUSIONS: We found a high rate of ocular inflammation control with infliximab therapy. The incidence of adverse effects in this study was low.

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Am J Ophthalmol. 2007 Jul;144(1):55-61.
Interferon-alpha as an effective treatment for noninfectious posterior uveitis and panuveitis.
Plskova J, Greiner K, Forrester JV.
Department of Ophthalmology, University of Aberdeen, Aberdeen, Scotland, United Kingdom.

PURPOSE: Several studies have shown the capacity of interferon-alpha (IFN-alpha) to control ocular Behçet disease. The authors aimed to determine whether IFN-alpha was effective in treating patients with severe, refractory sight-threatening intraocular inflammation (uveitis) from a wider range of causes, including Behçet disease. DESIGN: Prospective, interventional case series. METHODS: Twelve patients with sight-threatening uveitis that failed to respond to one or more immunosuppressive regimens were enrolled to this study. Recombinant human IFN-alpha-2b was administered subcutaneously daily, and the dose was adjusted according to the clinical response. Main outcome measures were visual acuity, clinical activity of uveitis (including binocular indirect ophthalmoscopy [BIO] score and presence or absence of macular edema), and adverse effects of the treatment. RESULTS: The mean observation period was 11 months (range, one to 29 months). A positive clinical response was observed in 83% of patients. Median visual acuity improved from 0.54 to 0.2 (logarithm of the minimum angle of resolution units; P < .001) and median BIO score decreased from 1.0 to 0.5 (P < .05) within one month of treatment. Macular edema, if present, resolved in all patients within days of treatment. The main adverse events were tiredness, lymphopenia, flu-like symptoms, and transient increase of liver enzymes. Weight loss occurred in four patients. Four patients experienced depression, one of them attempting suicide. Three patients experienced typical features of IFN-alpha-associated retinopathy, which resolved on reducing the dose. CONCLUSIONS: IFN-alpha seems to have significant potential in treatment of severe, sight-threatening refractory uveitis from a variety of causes. A range of adverse events, including IFN-alpha-associated retinopathy, may occur and could limit the use of this immunomodulatory drug.

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Klin Monatsbl Augenheilkd. 2007 Jun;224(6):538-42.
[Update on vitrectomy for pediatric uveitis.]
[Article in German]
Garweg JG, Becker M, Lommatzsch A, Bartz-Schmidt KU.
Swiss Eye Institute, Bern, Schweiz.

PURPOSE: The role of vitrectomy in pediatric uveitis has as yet not been established. Addressing this question has been reinforced since the recent introduction of the new and relatively well tolerated medical treatment options using biologicals, i. e. TNFalpha blocking agents. METHODS: A systematic review of literature has been supplemented by results of vitrectomy performed in 41 consecutive eyes of 33 children and adolescents at our institution and followed for 0.5 to 10 years. RESULTS: No single controlled study on the role of vitrectomy for uveitis has been identified. Beyond a total of 44 case series including 1762 eyes within the last 25 years, 3 papers specifically focussed on vitrectomy for pediatric uveitis including 73 eyes. This series included 29 eyes of our series. Published and recent own data indicate 2 specific findings consistent for all series: reduction of CME presence from 36 to 6.9 % with a resulting visual improvement in 79.1 % of cases and a quietening down of inflammatory activity postoperatively allowing to taper down or stop steroid and immunosuppressive therapy from preoperatively 80 and 30 % to approximately 30 and 10 %, respectively. CONCLUSION: In the absence of evidence-based results, the data from case series indicate that vitrectomy for pediatric uveitis at least meets the expectations from vitrectomy in adult forms of uveitis regarding the reduction of cystoid macular edema and required systemic steroid and immunosuppressive therapies.

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Klin Monatsbl Augenheilkd. 2007 Jun;224(6):532-7.
[Cataract surgery in childhood uveitis.]
[Article in German]
Szurman P, Heiligenhaus A, Hettlich HJ, Dick HB, Kohnen T.
Universitäts-Augenklinik, Eberhard-Karls-Universität, Tübingen.

The development of cataract is the most frequent vision-threatening complication of uveitis in children. In such cases cataract surgery is associated with a particular risk of intra- and postoperative complications and requires an intensive perioperative immunosuppression, an essentially atraumatic operation in a quiscient eye, and aggressive amblyopia treatment. When these factors are taken into consideration, a timely cataract operation can result in a sustained visual rehabilitation even for children with uveitis.

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Klin Monatsbl Augenheilkd. 2007 Jun;224(6):526-31.
[Inhibitors of Tumour Necrosis Factor-alpha for the Treatment of Arthritis and Uveitis in Childhood.]
[Article in German]
Heiligenhaus A, Horneff G, Greiner K, Mackensen F, Zierhut M, Foeldvari I, Michels H.
Augenabteilung am St. Franziskus Hospital, Münster; Universität Duisburg-Essen.

BACKGROUND: Chronic uveitis in childhood is a common complication of juvenile idiopathic arthritis (JIA) that frequently leads to loss of vision. Besides from corticosteroids and immunosuppressive drugs, Tumour necrosis factor-alpha (TNF-alpha) inhibitors are used frequently. MATERIALS AND METHODS: The literature published before September 2006 was evaluated for the usefulness of TNF-alpha inhibitors (etanercept, infliximab, adalimumab) for the treatment of JIA-associated uveitis. RESULTS: TNF-alpha inhibitors are effective drugs for the treatment of chronic uveitis in childhood. The response rate of uveitis in childhood to etanercept was approximately 50 %. However, disease recurrence, first manifestations of uveitis and new complications occurred during the treatment. Infliximab and adalimumab appear to be more effective for the treatment of uveitis in childhood than etanercept. CONCLUSIONS: The therapy with TNF-alpha inhibitors is expensive and increases the long-term risk for secondary diseases, such as tuberculosis and probably malignant lymphoma. Their use should be restricted to uveitis patients not responding to corticosteroids and at least one of established immunosuppressive drugs.

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Klin Monatsbl Augenheilkd. 2007 Jun;224(6):516-9.
[Topical and systemic corticosteroid therapy for uveitis in childhood.]
[Article in German]
Thurau SR, Frosch M, Zierhut M, Gümbel H, Heiligenhaus A.
Augenklinik der Ludwig-Maximilians-Universität, München.

Systemic and topical corticosteroids constitute an important part in the treatment of children with uveitis, because of their rapid therapeutic onset. Patients with anterior uveitis receive eye drops initially every 30 minutes or every hour. Children will experience the same side effects as adults but, in addition, there will be a growth retardation. Therefore, if treatment is required for extended periods of time it is important to avoid steroid quantities above the Cushing level and to initiate an additional systemic immunosuppressive treatment regimen early.

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Int Ophthalmol. 2007 May 8; [Epub ahead of print]
Tuberculous uveitis, a resurgent and underdiagnosed disease.
Cimino L, Herbort CP, Aldigeri R, Salvarani C, Boiardi L.
Department of Ophthalmology, Ospedale S.M. Nuova, Viale Risorgimento, 42100, Reggio Emilia, Italy, l.cimino@libero.it.

Background Over the last decade ocular involvement due to tuberculosis has re-emerged. In non-endemic areas the low frequency of active tuberculosis is at the origin of an underestimation of the disease. The purpose of this study is to report a group of patients with presumed tuberculous uveitis and to analyse the pre-diagnostic course, the diagnostic delay and the evolution of ocular inflammation after diagnosis and anti-tuberculous treatment. Methods Criteria for presumed tuberculous uveitis included the presence of a hyperpositive tuberculin skin test with compatible uveitis and the exclusion of other possible etiologies. Results Thirty-five patients fulfilled the diagnostic criteria for presumed tuberculous uveitis and were included in the study. The diagnosis was performed at presentation in only seven patients, while the correct diagnosis was delayed in the other 30 patients. The mean diagnostic delay was 5.7 +/- 4 years. Anti-tuberculous therapy was given for a minimum of 6 to a maximum of 24 months. Post-diagnostic mean follow-up was 30.4 +/- 13.4 months. Anti-tuberculous therapy resulted in a highly significant increase in visual acuity, from 0.53 to 0.78 (P < 0.001), a highly significant decrease of recurrences, from 100 to 10% (P < 0.001), with only three recurrences observed during the follow-up, and a highly significant decrease in intra-ocular pressure, from 18.3 to 13.7 (P < 0.001). Conclusions Our study tends to confirm the existence of tuberculous uveitis and supports the validity of the proposed diagnostic criteria. Recognition of the correct diagnosis and specific therapy, even with substantial delay, avoids recurrences, improves visual acuity and intra-ocular inflammation and decreases intra-ocular pressure.

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Ophthalmology. 2007 May;114(5):1000-6.
Long-term efficacy and tolerance of tacrolimus for the treatment of uveitis.
Hogan AC, McAvoy CE, Dick AD, Lee RW.
Bristol Eye Hospital, Bristol, United Kingdom.

PURPOSE: To evaluate the long-term efficacy and tolerance of tacrolimus for the treatment of uveitis. DESIGN: Retrospective case series. PARTICIPANTS: Sixty-two consecutive patients with noninfectious uveitis treated with tacrolimus at a single academic referral center between April 2000 and April 2004. METHODS: A standard data set was obtained from patients' medical records and analyzed according to the recommendations of the Standardization of Uveitis Nomenclature Working Group. MAIN OUTCOME MEASURES: (1) Rate of tapering oral prednisone to 10 mg daily, (2) requirement for alternative second-line immunosuppressive therapy, and (3) rate of tacrolimus dose reduction or discontinuation due to side effects. RESULTS: In this cohort with well-established ocular inflammation, patients successfully tapered their oral prednisone to 10 mg daily at an average rate of 1.62 per patient-year (PY), with an 85% probability of achieving < or =10 mg after 1 year 2 months of treatment. Tacrolimus was discontinued due to intolerance at a rate of 0.13/PY. This was predominantly due to noncardiovascular adverse events, and rates of introducing or increasing concomitant treatment for hypertension, hypercholesterolemia, and diabetes mellitus were all below 0.05/PY. Creatinine rises of > or =30% were also notably uncommon (0.05/PY). CONCLUSION: Tacrolimus's efficacy for the treatment of uveitis is maintained long-term, and its cardiovascular risk profile is excellent.

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Klin Monatsbl Augenheilkd. 2007 Apr;224(4):367-72.
[Options and strategy for the treatment of chronic endogenous uveitis]
[Article in German]
Garweg JG.
Swiss Eye Institute, Augenklinik am Lindenhofspital, Bern, Schweiz. justus.garweg@eye-institute.ch

PURPOSE: The treatment of chronic endogenous uveitis has included the use of local and systemic corticosteroids since the early 1950 s, and these still constitute the first-line option in the treatment, once an infectious aetiology has been excluded. METHODS: Since the 1960 s, broad experience has been collected with antiproliferative and alkylating agents, and since the 1980 s several immunosuppressants have been employed in the therapy for endogenous uveitis. It has been recognised that the therapeutic response is not only related to a specific uveitic entity, but also to the genetic background of the individual. RESULTS: Therefore, no clear guide lines for therapy exist and, for most of the drugs, controlled studies are not available. Vitrectomy and intravitreal drug delivery have been added as local options on top or in case of failure of systemic therapies. The advent of biological agents, however, i. e. the introduction of interferon alpha and TNF alpha blocking agents, has opened a new era in the treatment of immunogenetic and autoimmune disorders. CONCLUSION: Evidence-based knowledge and personal experience have been reviewed to provide an update on the therapeutic strategy for chronic endogenous uveitis. The newly introduced biologicals seem to represent an interesting addition to the existing therapeutic options. Informations pertaining to efficacy and side effects of a long-term treatment of uveitis are, nevertheless, as yet not available.

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J Rheumatol. 2007 Mar 1; [Epub ahead of print]
Tumor Necrosis Factor-alpha Blocker in Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to Second-line Agents: Results of a Multinational Survey.

Foeldvari I, Nielsen S, Kummerle-Deschner J, Espada G, Horneff G, Bica B, Olivieri AN, Wierk A, Saurenmann RK.
>From the Department of Pediatric Rheumatology, Hamburger Zentrum fur Kinder und Jugendrheumatologie, Klinikum Eilbek, Hamburg, Germany; Julinae Marie Centret, Righospitalet, Copenhagen, Denmark; Department of Pediatric Rheumatology, Universitatskinderklinik, Tubingen, Germany; Department of Pediatric Rheumatology, Ricardo Gutierrez Children's Hospital, Buenos Aires, Argentina; Department of Pediatrics and Neonatology, Klinik Sankt Augustin, Sank Augustin, Germany; Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Pediatrics, Seconda Universita di Napoli, Napoli, Italy; Pediatric Rheumatology Clinic, Allgemeinen Krankenhaus Eilbek, Hamburg, Germany; and University Children's Hospital Zurich, Zurich, Switzerland.

OBJECTIVE: Uveitis occurs in 10%-15% of patients with juvenile idiopathic arthritis (JIA). If topical treatment fails, second-line agents are used to control the disease. However, some patients need the addition of tumor necrosis factor-a (TNF-a) antagonist (anti-TNF). We organized a cross-sectional cohort to investigate use and efficacy of anti-TNF treatment in patients with JIA-associated uveitis. METHODS: The international pediatric rheumatology community was queried about the use and efficacy of anti-TNF in treatment of JIA-associated uveitis using an E-mail survey. RESULTS: Of the 33 responding centers following 884 patients with uveitis, only 15 centers, following 404 patients, were using anti-TNF for this indication. A total of 47 patients with JIA-related uveitis treated with anti-TNF because of an insufficient response to previous therapy were reported. The mean age of the patients was 12.5 years. The mean duration from onset of uveitis to start of anti-TNF treatment was 45.1 months. Three different anti-TNF agents were used: etanercept in 34 cases, infliximab in 25 cases, and adalimumab in 3 cases. In 12 of the 34 patients etanercept was inefficacious and patients were switched to infliximab. The final response was rated according to a composite index as 53%/12%/32%, and according to physician rating as 47%/12%/38% representing good, moderate, and poor, respectively, in the etanercept group; and 70%/30%/0% and 68%/24%/0% in the infliximab group. All 3 patients taking adalimumab were responders. Infliximab was statistically significantly more efficacious for the treatment of JIA-associated uveitis than etanercept (chi-square p = 0.004). CONCLUSION: Anti-TNF seems to be an effective treatment for refractory JIA-associated uveitis. In this cohort infliximab was more efficacious than etanercept.

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Ann Pharmacother. 2007 Mar 6; [Epub ahead of print]
Retisert: Is the New Advance in Treatment of Uveitis a Good One?
Mohammad DA, Sweet BV, Elner SG.
General Pharmacy Practice Resident, University of Michigan Health System and College of Pharmacy, University of Michigan, Ann Arbor, MI.

OBJECTIVE: To review the use of corticosteroids for the treatment of uveitis, with a focus on the pharmacology, efficacy, and safety of a newer delivery device, Retisert. DATA SOURCES: A PubMed/MEDLINE search from 1950 through February 2007 was conducted, and manufacturer-provided data were reviewed. STUDY SELECTION AND DATA EXTRACTION: Animal studies and Phase II and III clinical trials evaluating the safety and efficacy of Retisert for the treatment of uveitis were considered. The data were extracted from PubMed/MEDLINE using the search terms fluocinolone acetonide, corticosteroids, intravitreal implant, uveitis, ocular steroids, and Retisert. DATA SYNTHESIS: The findings of the clinical studies showed, with use of Retisert, a reduction in the recurrence of uveitis, improvement in visual acuity, and a decreased need for adjunctive therapy with corticosteroids and immunosuppressant agents. There are currently no studies directly comparing Retisert with other treatment options. The most commonly reported adverse events (ADEs) in clinical trials included cataracts, increased intraocular pressure, post-procedural complications associated with implant insertion, and ocular pain. Other ocular ADEs included decreased visual acuity, glaucoma, blurred vision, an abnormal sensation in the eye, eye irritation, and a change in tearing. These ADEs are similar to those seen with chronic corticosteroid therapy delivered by other ocular routes. CONCLUSIONS: Retisert implants have been shown to deliver sufficient drug for a longer period of time compared with the traditional steroid delivery methods. Promising efficacy results show a significant reduction in recurrence rate and improvement in visual acuity for approximately 3 years after implant. However, the drug carries the risks associated with the implant procedure and with chronic exposure of the eye to steroids. Until more data on the long-term safety are known, Retisert should be reserved for patients who are no longer tolerant of or responsive to more traditional treatment modalities. ((CE)) This article is approved for continuing education credit. ACPE UNIVERSAL PROGRAM NUMBER: 407-000-07-010-H01.

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Br J Ophthalmol. 2007 Feb 21; [Epub ahead of print]
Outcome of phacoemulsification in patients with uveitis.
Elgohary MA, McCluskey P, Towler HM, Okhravi N, Singh R, Obikpo R, Lightman S.
Moorfields Eye Hospital, United Kingdom.

PURPOSE: To examine the visual outcome and identify risk factors for developing postoperative uveitis, macular oedema and Nd:YAG capsulotomy after phacoemulsification and intraocular lens (IOL) implantation in patients with uveitis. METHOD: This is a retrospective review of the medical records of 101 eyes of 101 patients. One eye was randomly selected for inclusion in patients who had bilateral surgery. Patients with juvenile arthritis, kerato-uveitis and lymphoma-associated uveitis were excluded. RESULTS: At the first postoperative and final visits, visual acuity was significantly better (p<0.001) and 64.4% and 71.3% of patients, respectively, achieved >=2 lines of visual improvement. The cumulative probability of doubling of the visual angle was 52% over 6 years of follow-up and this occurred at a higher rate in the presence of preoperative retinal or optic nerve lesions [HR=4.49; 95% confidence interval (CI) (1.41 to 14.29)]. Within 3 months postoperatively, uveitis was more likely in female patients [OR=6.21 (1.41, 27.43)] and in the presence of significant intra-operative posterior synechiae [OR=8.43 (1.09, 65.41)]; and macular oedema was more likely in patients who developed postoperative uveitis [OR=7.45 (1.63, 34.16)]. Nd:YAG capsulotomy occurred at a higher rate in patients aged 55 years or younger [HR=2.28; 95% CI (1.06, 4.93)] and in those with hydrogel IOLs [HR=3.71(1.04, 13.20)] and at a lower rate in patients who had prophylactic systemic corticosteroids [HR=0.25 (0.11, 0.59)], with plate-haptic silicone IOLs [HR=0.23 (0.08, 0.64)] and 3- piece silicone IOLs [HR=0.19 (0.05, 0.74)] in comparison with PMMA IOLs. CONCLUSION: The majority of patients with uveitis achieve improvement of visual acuity after phacoemulsification but an increasing rate of visual loss occurs in those with pre-existent macular or optic nerve lesions. Identifying patients at risk of postoperative complications should help in patient counselling and to pre-empt these complications by using preoperative prophylactic corticosteroids, careful IOL selection and postoperative intensive corticosteroids.

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J Pediatr Ophthalmol Strabismus. 2007 Jan-Feb;44(1):28-34.
Immunosuppressants used in a steroid-sparing strategy for childhood uveitis.
Schatz CS, Uzel JL, Leininger L, Danner S, Terzic J, Fischbach M.
Strasbourg University Eye Hospital, BP 426 1 place de l'Hopital, 67091 Strasbourg, France.

PURPOSE: To review, with respect to etiology, the efficacy and complications of different immunosuppressants used in a steroid-sparing strategy for children with uveitis. PATIENTS AND METHODS: Forty children with uveitis were observed during a 5-year period, from 1997 to 2002. After complete ocular and physical assessment, routine and specific laboratory investigations were conducted along with radiologic examination. All cases underwent local therapy. Systemic corticosteroids were necessary in 75% of cases. Pediatric staff determined the need for initial association or sequential relay with immunosuppressants, depending on the severity of the uveitis. A steroid-sparing strategy was developed. RESULTS: The average age was 6.5 years (range, 3 months to 14 years), with a male-to-female ratio of 23 to 17. Uveitis was anterior in 55% of cases, intermediate in 2.5%, posterior in 42.5%, and bilateral in 62.5%. A positive etiology was found in 47.5% of cases, and articular symptoms were present in 25%. Overall, the improvement in visual acuity was 62.2%. Where corticotherapy was associated with azathioprine, a 61% improvement was achieved. Corticosteroid therapy associated with mycophenolate mofetil resulted in a 94% improvement. No complications were present in 42.5% of cases. Ocular complications were present in 57.5% of cases and systemic complications were present in 12.5% of cases, none being directly related to the use of steroids. CONCLUSION: The association of systemic corticotherapy and immunosuppressants in pediatric relapsing or steroid-dependent uveitis allows good recovery of visual acuity, fewer complications, and a minimization of side effects, especially those related to systemic corticosteroids. It requires close collaboration between the ophthalmologist and a fully involved pediatrician.

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Br J Ophthalmol. 2007 Jan 3; [Epub ahead of print]
Outcome of Phacoemulsification in Patients with Uveitis.
Elgohary MA, McCluskey PJ, Towler HM, Okhravi N, Singh RP, Obikpo R, Lightman SS.
Moorfields Eye Hospital, United Kingdom.

PURPOSE: To examine the visual outcome and identify risk factors for developing postoperative uveitis, macular oedema and Nd:YAG capsulotomy after phacoemulsification (PE) and intraocular lens (IOL) implantation in patients with uveitis. METHOD: This is a retrospective review of the medical records of 101 eyes of 101 patients. One eye was randomly selected for inclusion in patients who had bilateral surgery. Patients with juvenile arthritis, kerato-uveitis and lymphoma-associated uveitis were excluded. RESULTS: At the postoperative and final visits, visual acuity was significantly better (p<0.001) and 64.4% and 71.3% of patients, respectively, achieved >=2 lines of visual improvement. Doubling of the visual angle occurred in 52% of patients over 6 years of follow- up and at a higher rate in the presence of preoperative retinal or optic nerve lesions [HR=4.49; 95% confidence interval (CI) (1.41 to 14.29)]. Within 3 months postoperatively, uveitis was more likely in female patients [OR=6.21 (1.41, 27.43)] and in the presence of significant intra-operative posterior synechiae [OR=8.43 (1.09, 65.41)]; and macular oedema was more likely in patients who developed postoperative uveitis [OR=7.45 (1.63, 34.16)]. Nd:YAG capsulotomy occurred at a higher rate in patients aged 55 years or younger [HR=2.28; 95% CI (1.06, 4.93)] and in those with hydrogel IOLs [HR=3.71 (1.04, 13.20)] and at a lower rate in patients who had prophylactic systemic corticosteroids [HR=0.25 (0.11, 0.59)], with plate-haptic silicone IOLs [HR=0.23 (0.08, 0.64)] and 3-piece silicone IOLs [HR=0.19 (0.05, 0.74)] in comparison with PMMA IOLs. CONCLUSION: The majority of patients with uveitis achieve improvement of their visual acuity after phacoemulsification but an increasing rate of doubling of the visual angle occurs in patients with pre-existent macular or optic nerve lesions. The use of prophylactic steroids, careful IOL selection and postoperative intensive steroids in patients at risk should help reduce postoperative complications and plan their follow- up.

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J Ocul Pharmacol Ther. 2006 Dec;22(6):431-6.
Oral Echinacea purpurea extract in low-grade, steroid-dependent, autoimmune idiopathic uveitis: a pilot study.
Neri PG, Stagni E, Filippello M, Camillieri G, Giovannini A, Leggio GM, Drago F.
Department of Neurosciences - Ophthalmology Section, Polytechnic University of Marche, Ancona, Italy.

AIM: The aim of to test efficacy and safety of Echinacea purpurea (echinacea) extract in the control of low-grade uveitis. METHODS: Fifty-one (51) patients with low-grade, steroid dependent, autoimmune uveitis were recruited; posterior uveitis was excluded. The start therapy was represented by topical desamethazone for anterior uveitis and oral prednisone, rapidly tapered, for anterior uveitis with inflammatory scores equal to +2 and in all cases of intermediate uveitis. Best-corrected visual acuity (BCVA) decrease or improvement was defined as a reduction or increase of 2 or more letters seen from the initial BCVA; ETDRS chart was used. Thirty-two (32) patients (21 with anterior uveitis and 11 with intermediate uveitis) received Echinacea (150 mg twice/day) as add-on therapy, whereas 20 patients (10 with anterior uveitis and 9 with intermediate uveitis) were treated with the conventional steroid therapy alone. RESULTS: Thirty-one (31) patients showed anterior uveitis and 20 intermediate uveitis. The follow-up duration was 9 months. At the last follow-up, 19/21 patients with anterior uveitis and 9/11 with intermediate uveitis treated with echinacea presented uveitis settled, with a steroid-off time of 209 and 146 days, respectively. BCVA was stable or improved in 19/21 of anterior uveitis and 9/11 of intermediate uveitis. No adverse reactions supposed to be resulting from commercial-grade echinacea were recorded. Patients who did not receive echinacea required a longer treatment period with steroids with a steroid-off time of 121 and 87 days. CONCLUSIONS: Systemic echinacea appears safe and effective in the control of low-grade autoimmune idiopathic uveitis

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Curr Rheumatol Rep. 2006 Dec;8(6):459-68.
Ocular complications of childhood rheumatic diseases: uveitis.
Reiff A.
Division of Rheumatology, Children's Hospital Los Angeles, CA 90027, USA. reiff@hsc.usc.edu

Ocular involvement is common in pediatric rheumatologic diseases, supporting the concept that these conditions cannot be understood simply as isolated entities, but rather as multisystem disorders. The reasons for the breach of the eye-brain barrier and the targeting of the usually well-shielded eye during a pan-inflammatory process remains unclear. Pediatric rheumatologists should become familiar with these ocular disorders, because as important members of the treatment team, they manage more serious cases of inflammatory eye disease. A close collaboration between the treating rheumatologist and the ophthalmologist is essential to prevent potentially devastating outcomes. Therapeutic interventions such as topical steroids, systemic immunosuppressants, and biologics must balance the necessity of controlling ocular inflammation and the adverse effects of these treatments on a growing child.
 

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